The Hedgehog (Hh) signaling pathway plays a critical role in development and tumorigenesis across metazoa. Three mammalian Hh genes have been identified: Sonic hedgehog (SHh), Desert hedgehog (DHh), and Indian hedgehog (IHh). These proteins are secreted proteins that act by antagonizing the receptor Patched (Ptch1 or Ptch2 in humans). Ptch acts in part by antagonizing the activity of Smoothened (Smo), a G-protein coupled receptor that activates the transcription factor Gli. When Shh binds to Ptch, Ptch-mediated repression of Smo is relieved, allowing Smo to promote Gli-dependent transcription. During development, Hh induced Smo activity promotes proliferation, migration, and differentiation of progenitor cells to pattern organ development. However, disregulation of Hh pathway signaling, for example by inactivating mutations of Ptch or activating mutations of Smo, has been associated with cancer (Toftgard, R. Hedgehog signalling in cancer. Cell Mol. Life Sci., 57: 1720-1731 (2000)). Induction of Hh target genes is required for tumor growth and maintenance in tumor epithelia, and Hh pathway signaling has been implicated in tumor metastasis of a number of epithelial tumors. For example, basal cell carcinoma (BCC) initiation and expansion requires high levels of Hh pathway signaling. What is needed are novel regulators of the Hedgehog signaling pathway. The present invention addresses these issues.